Activation of CD11b+ Kupffer cells/macrophages as a common cause for exacerbation of TNF/Fas-ligand-dependent hepatitis in hypercholesterolemic mice.
Activation of CD11b+ Kupffer cells/macrophages as a common cause for exacerbation of TNF/Fas-ligand-dependent hepatitis in hypercholesterolemic mice.
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DOI：
10.1371/journal.pone.0049339
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Seki S
中科院分区：
文献类型：
--
作者：
Nakashima H;Ogawa Y;Shono S;Kinoshita M;Nakashima M;Sato A;Ikarashi M;Seki S
本文报道了α-半乳糖神经酰胺（α-GalCer）或细菌DNA基序（CpG-ODN）诱导的小鼠肝损伤是通过TNF/NKT细胞/Fas配体（FasL）途径介导的。此外，F4/80+ Kupffer细胞可细分为具有吞噬能力的CD 68+亚群和具有TNF产生能力的CD 11b+亚群。如果小鼠喂食高脂肪和胆固醇饮食（HFCD），则CD 11b+亚群增加。本研究探讨了HFCD如何影响NKT细胞和F4/80+ CD 11b+亚群的功能以及这些肝炎模型。在C57 BL/6小鼠接受HFCD、高胆固醇饮食（HCD）、高脂肪饮食（HFD）和对照饮食（CD）四周后，与CD小鼠相比，HFCD小鼠增加了CD 11b+群体的表面CD 1d和细胞内TLR-9表达。α-GalCer和CpG-ODN诱导的HCD和HFCD小鼠肝损伤均较CD小鼠严重，且与血清TNF水平成正比。此外，肝脏胆固醇水平而不是血清胆固醇水平或肝脏甘油三酯水平参与肝炎的加重。两种试剂诱导的HFCD小鼠NKT细胞FasL表达上调。此外，HFCD小鼠的肝脏单个核细胞和纯化的F4/80+ CD 11b+亚群在体外用两种试剂刺激产生的TNF比CD小鼠产生的TNF更大量。证实了F4/80+ CD 11b+细胞中的细胞内TNF产生。因此，HFCD增加的F4/80+ CD 11b + Kupffer细胞/巨噬细胞数量及其增强的TNF产生在TNF/NKT细胞/FasL依赖性肝损伤中起关键作用。
We have reported that the mouse hepatic injury induced by either α-galactosylceramide (α-GalCer) or bacterial DNA motifs (CpG-ODN) is mediated by the TNF/NKT cell/Fas-ligand (FasL) pathway. In addition, F4/80+ Kupffer cells can be subclassified into CD68+ subset with a phagocytosing capacity and CD11b+ subset with a TNF-producing capacity. CD11b+ subset increase if mice are fed high-fat and cholesterol diet (HFCD). The present study examined how a HFCD affects the function of NKT cells and F4/80+ CD11b+ subset and these hepatitis models. After the C57BL/6 mice received a HFCD, high-cholesterol diet (HCD), high-fat diet (HFD) and control diet (CD) for four weeks, the HFCD mice increased surface CD1d and intracellular TLR-9 expression by the CD11b+ population compared to CD mice. Hepatic injury induced either by α-GalCer or CpG-ODN was more severe in HCD and HFCD mice compared to CD mice, which was in proportion to the serum TNF levels. In addition, liver cholesterol levels but not serum cholesterol levels nor liver triglyceride levels were involved in the aggravation of hepatitis. The FasL expression of NKT cells induced by both reagents was upregulated in HFCD mice. Furthermore, the liver mononuclear cells and purified F4/80+ CD11b+ subset from HFCD mice stimulated with either reagent in vitro produced a larger amount of TNF than did those from CD mice. Intracellular TNF production in F4/80+ CD11b+ cells was confirmed. The increased number of F4/80+ CD11b+ Kupffer cells/macrophages by HFCD and their enhanced TNF production thus play a pivotal role in TNF/NKT cell/FasL dependent hepatic injury.
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影响因子：
3.8
作者：
Jaeschke, H;Gores, GJ;Lemasters, JJ
通讯作者：
Lemasters, JJ
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DOI：
10.1161/atvbaha.108.179705
发表时间：
2012-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
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通讯作者：
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作者：
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影响因子：
25.7
作者：
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13.5
作者：
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